tbuckley/cabot-search huggingface dataset:
Nonalcoholic Fatty Liver Disease Without Metabolic-associated Fatty Liver Disease and the Risk of Metabolic Syndrome
Authors: Dong Hyun Sinn, Danbee Kang, Sung Chul Choi, Yun Soo Hong, Di Zhao, Eliseo Guallar, Yewan Park, Juhee Cho, Geum-Youn Gwak
Journal: Clinical Gastroenterology and Hepatology (2022)

Metabolic (dysfunction)-associated fatty liver disease (MAFLD) was proposed to replace nonalcoholic fatty liver disease (NAFLD). Some people fulfill diagnostic criteria of NAFLD but not MAFLD (NAFLD without MAFLD), but the clinical implications of NAFLD in these subjects is unknown.We followed cohort of 12,197 men and women 20 years of age or older without metabolic dysfunction (defined by MAFLD criteria), heavy alcohol use, chronic viral hepatitis, liver cirrhosis, or malignancy for their risk of incident metabolic syndrome defined by Adult Treatment Panel III criteria.By design, none of the study participants had MAFLD at baseline. The prevalence of NAFLD among participants without metabolic dysfunction meeting MAFLD criteria and without significant alcohol intake was 7.6%. During 74,508 person-years of follow-up, 2179 participants developed metabolic syndrome. The fully adjusted hazard ratio for metabolic syndrome comparing participants with NAFLD to those without it was 1.61 (95% confidence interval, 1.42-1.83). The increased risk of incident metabolic syndrome associated with NAFLD persisted for all studied subgroups, and the association was stronger for those with increased waist circumference (P for interaction = .029) and those without elevated triglycerides levels (P for interaction = .047).In this large cohort, participants with NAFLD without MAFLD were at higher risk of developing metabolic syndrome compared to participants with no NAFLD and no MAFLD. Using MAFLD criteria may miss opportunities for early intervention in these subjects.
Gastrointestinal Bleeding Risk With Direct Oral Anticoagulants: A Close Look at Drug Dose
Authors: Xiaoze Wang, Li Yang
Journal: Clinical Gastroenterology and Hepatology (2022)

We read with great interest the recently published original article by Ingason et al.1 This national population-based cohort study emphasized warfarin was associated with higher rates of upper gastrointestinal bleeding (GIB) but not lower or overall GIB compared with direct oral anticoagulants (DOACs). The results suggest that DOACs may be preferable to warfarin in patients with a history of peptic ulcer disease or major upper GIB. However, there are a few issues with the study that need to be discussed.
Differential effects of oestrogen on class-switch recombination of B cells dependent on sex chromosome complement: a cross-sectional study
Authors: Hannah Peckham, Anna Radziszewska, George Robinson, Lucia Martin-Gutierrez, Nina M De Gruijter, Gary Butler, Elizabeth C Jury, Elizabeth C Rosser, Coziana Ciurtin
Journal: The Lancet Rheumatology (2022)
Catch bond-inspired hydrogels with repeatable and loading rate-sensitive specific adhesion
Authors: Zuoying Yuan, Xiaocen Duan, Xing Su, Zhuoling Tian, Anqi Jiang, Zhuo Wan, Hao Wang, Pengfei Wei, Bo Zhao, Xiaozhi Liu, Jianyong Huang
Journal: Bioactive Materials (2022)

Biological receptor-ligand adhesion governed by mammalian cells involves a series of mechanochemical processes that can realize reversible, loading rate-dependent specific interfacial bonding, and even exhibit a counterintuitive behavior called catch bonds that tend to have much longer lifetimes when larger pulling forces are applied. Inspired by these catch bonds, we designed a hydrogen bonding-meditated hydrogel made from acrylic acid-N-acryloyl glycinamide (AA-NAGA) copolymers and tannic acids (TA), which formed repeatable specific adhesion to polar surfaces in an ultra-fast and robust way, but hardly adhered to nonpolar materials. It demonstrated up to five-fold increase in shear adhesive strength and interfacial adhesive toughness with external loading rates varying from 5 to 500 mm min-1. With a mechanochemical coupling model based on Monte Carlo simulations, we quantitatively revealed the nonlinear dependence of rate-sensitive interfacial adhesion on external loading, which was in good agreement with the experimental data. Likewise, the developed hydrogels were biocompatible, possessed antioxidant and antibacterial properties and promoted wound healing. This work not only reports a stimuli-responsive hydrogel adhesive suitable for multiple biomedical applications, but also offers an innovative strategy for bionic designs of smart hydrogels with loading rate-sensitive specific adhesion for various emerging areas including flexible electronics and soft robotics.
Polyethylene glycol (PEG): The nature, immunogenicity, and role in the hypersensitivity of PEGylated products
Authors: Mohamed Ibrahim, Eslam Ramadan, Nehal E. Elsadek, Sherif E. Emam, Taro Shimizu, Hidenori Ando, Yu Ishima, Omar Helmy Elgarhy, Hatem A. Sarhan, Amal K. Hussein, Tatsuhiro Ishida
Journal: Journal of Controlled Release (2022)
Short-course antibiotic therapy for hospitalized patients with early clinical response in community-acquired pneumonia: a multicentre cohort study
Authors: Simone Bastrup Israelsen, Markus Fally, Britta Tarp, Lilian Kolte, Pernille Ravn, Thomas Benfield
Journal: Clinical Microbiology and Infection (2022)

To explore whether short-course antibiotic therapy is efficient and safe in routine clinical settings among patients hospitalized with community-acquired pneumonia (CAP) who achieve an early clinical response.During 2017-2019, we conducted a cohort study of patients admitted with CAP to four hospitals in Denmark. Data were prospectively gathered from medical records and enriched with data from nationwide registries. In the present study, we included patients with early clinical response and divided them into treatment groups based on antibiotic duration, as decided by the attending physician: short-course (4-7 days) or prolonged-course (8-14 days). The primary outcome was post-treatment mortality within 30 days. Secondary outcomes included readmissions or new antibiotics. Logistic regression models were used to estimate ORs with 95% CIs, and inverse probability weighting was applied to adjust for confounding.The study cohort included 1151 patients with a median age of 74 years, predominantly presenting with mild-moderate disease. The 30-day post-treatment mortality was 3.36% (11/327) in the short-course group and 3.40% (28/824) in the prolonged-course group (adjusted OR 1.05, 95% CI 0.38-1.88). Readmission occurred in 15.6% (42/269) vs. 14.0% (102/727) (adjusted OR 1.07, 95% CI 0.75-1.69) and new prescription of antibiotics in 11.9% (32/269) vs. 12.1% (88/727) (adjusted OR 0.99, 95% CI 0.61-1.49).In patients hospitalized with CAP and early clinical response, similar outcomes were observed between short-course and prolonged-course therapies. These results support the use of short-course therapy in routine clinical settings.
Epigenetic and immunological indicators of IPEX disease in subjects with FOXP3 gene mutation
Authors: Mansi Narula, Uma Lakshmanan, Simon Borna, Janika J. Schulze, Tyson H. Holmes, Nicholas Harre, Matthew Kirkey, Akshaya Ramachandran, Veronica Maria Tagi, Federica Barzaghi, Eyal Grunebaum, Julia E.M. Upton, Vy Hong-Diep Kim, Christian Wysocki, Victoria R. Dimitriades, Kenneth Weinberg, Katja G. Weinacht, Yael Gernez, Bindu K. Sathi, Magdalena Schelotto, Matthew Johnson, Sven Olek, Christoph Sachsenmaier, Maria-Grazia Roncarolo, Rosa Bacchetta
Journal: Journal of Allergy and Clinical Immunology (2022)

Forkhead box protein 3 (FOXP3) is the master transcription factor in CD4+CD25hiCD127lo regulatory T (Treg) cells. Mutations in FOXP3 result in IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) syndrome. Clinical presentation of IPEX syndrome is broader than initially described, challenging the understanding of the disease, its evolution, and treatment choice.We sought to study the type and extent of immunologic abnormalities that remain ill-defined in IPEX, across genetic and clinical heterogeneity.We performed Treg-cell-specific epigenetic quantification and immunologic characterization of severe "typical" (n = 6) and "atypical" or asymptomatic (n = 9) patients with IPEX.Increased number of cells with Treg-cell-Specific Demethylated Region demethylation in FOXP3 is a consistent feature in patients with IPEX, with (1) highest values in those with typical IPEX, (2) increased values in subjects with pathogenic FOXP3 but still no symptoms, and (3) gradual increase over the course of disease progression. Large-scale profiling using Luminex identified plasma inflammatory signature of macrophage activation and TH2 polarization, with cytokines previously not associated with IPEX pathology, including CCL22, CCL17, CCL15, and IL-13, and the inflammatory markers TNF-α, IL-1A, IL-8, sFasL, and CXCL9. Similarly, both Treg-cell and Teff compartments, studied by Mass Cytometry by Time-Of-Flight, were skewed toward the TH2 compartment, especially in typical IPEX.Elevated TSDR-demethylated cells, combined with elevation of plasmatic and cellular markers of a polarized type 2 inflammatory immune response, extends our understanding of IPEX diagnosis and heterogeneity.
Endoscopy International Open – recently published
Journal: Endoscopy (2022)

Comment on: Learning curves in ERCP during advanced endoscopy training: a Canadian multicenter prospective study Endosc Int Open 2022; 10(09): E1174-E1180DOI: 10.1055/a-1795-9037 Comment on: Endoscopic electroincision of challenging benign biliopancreatic stricturesEndosc Int Open 2022; 10(09): E1297-E1301DOI: 10.1055/a-1871-8699 Comment on: Gel immersion endoscopic submucosal dissection: clinical experience with 13 cases of superficial esophageal cancerEndosc Int Open 2022; 10(09): E1302-E1306DOI: 10.1055/a-1894-0719
Zoonotic concerns of Marburg virus: Current knowledge and counteracting strategies including One Health approach to limit animal-human interface: An update
Authors: Kuldeep Dhama, Deepak Chandran, Sandip Chakraborty, Mohd Iqbal Yatoo, Md Aminul Islam, Manojit Bhattacharya, Chiranjib Chakraborty, Harapan Harapan, Wanpen Chaicumpa
Journal: International Journal of Surgery (2022)
Roles of effective stabilizers in improving oral bioavailability of naringenin nanocrystals: Maintenance of supersaturation generated upon dissolution by inhibition of drug dimerization
Authors: Guangshuai Zhang, Haishan Guan, Jianfeng Li, Mo Li, Xiaofan Sui, Baocheng Tian, Huiming Dong, Bingyang Liu, Zhonggui He, Ning Li, Mingming Zhao, Qiang Fu
Journal: Asian Journal of Pharmaceutical Sciences (2022)
Mimicking natural cholesterol assimilation to elevate the oral delivery of liraglutide for type II diabetes therapy
Authors: Ruinan Wu, Zhanghan Wu, Liyun Xing, Xi Liu, Lei Wu, Zhou Zhou, Lian Li, Yuan Huang
Journal: Asian Journal of Pharmaceutical Sciences (2022)

Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are a series of polypeptides broadly applied in the long-term treatment of type Ⅱ diabetes. However, administration of GLP-RA is mainly through repetitive subcutaneous injection, which may seriously decrease the compliance and safety. Herein, a bio-inspired oral delivery system was designed to enhance the oral absorption of liraglutide (Lira), a kind of GLP-1 RA, by mimicking the natural cholesterol assimilation. 25-hydroxycholesterol (25HC), a cholesterol derivative, was modified on the surfaced of Lira-loaded PLGA nanoparticles (Lira 25HC NPs) and functioned as a "top-down" actuator to facilitate unidirectional transcytosis across the intestinal epithelium. After oral delivery, Lira 25HC NPs displayed improved therapeutic effect as compared with oral free Lira on type Ⅱ diabetes db/db mice, as evidenced by multiple relieved diabetic symptoms including the enhanced glucose tolerance, repressed weight growth, improved liver glucose metabolism, decreased fasting blood glucose, HbA1c, serum lipid, and increased β cells activity. Surprisingly, the fasting blood glucose, liver glucose metabolism, and HbA1c of oral Lira-loaded 25HC NPs were comparable to subcutaneous injection of free Lira. Further mechanisms revealed that 25HC ligand could mediate the nanoparticles to mimic natural cholesterol absorption by exerting high affinity towards apical Niemann-Pick C1 Like 1 (NPC1L1) and then basolateral ATP binding cassette transporter A1 (ABCA1) overexpressed on the opposite side of intestinal epithelium. This cholesterol assimilation-mimicking strategy achieve the unidirectional transport across the intestinal epithelium, thus improving the oral absorption of liraglutide. In general, this study established a cholesterol simulated platform and provide promising insight for the oral delivery of GLP-1 RA.
Disposable Plastic Breathing Bags and Tubes
Authors: John B. Parmley
Journal: JAMA (1971)

Disposable units consisting of plastic masks, reservoir bags, and breathing tubes have been introduced to obviate hazards of cross-infection in anesthesia and inhalation therapy equipment. These are composed of polyethylene plastic that does not stretch after full inflation. Pressures exceeding 250 cm H<sub>2</sub>O may develop in these units. Such pressures are transmitted to the airway and pose hazards. Rupture of intrapulmonary structures, cardiac tamponade, and other adverse effects may result. Pressures of such magnitude do not develop in all-rubber units. Reservoir bags in disposable units for anesthesia and inhalation therapy should be composed of rubber or other material having the distensibility of rubber.
ARNEO: A Randomized Phase II Trial of Neoadjuvant Degarelix with or Without Apalutamide Prior to Radical Prostatectomy for High-risk Prostate Cancer
Authors: Gaëtan Devos, Lorenzo Tosco, Marcella Baldewijns, Thomas Gevaert, Karolien Goffin, Valentin Petit, Cindy Mai, Annouschka Laenen, Yannic Raskin, Carl Van Haute, Lieven Goeman, Gert De Meerleer, Charlien Berghen, Wout Devlies, Frank Claessens, Hendrik Van Poppel, Wouter Everaerts, Steven Joniau
Journal: European Urology (2022)
How Advanced Imaging Will Guide Therapeutic Strategies for Patients with Newly Diagnosed Prostate Cancer in the Years to Come
Authors: Melline G M Schilham, Mark Rijpkema, Tom Scheenen, Rick Hermsen, Jelle O Barentsz, J P Michiel Sedelaar, Heidi Kusters-Vandevelde, Linda G W Kerkmeijer, Diederik M Somford, Martin Gotthardt
Journal: European Urology (2022)
Mitapivat in adult patients with pyruvate kinase deficiency receiving regular transfusions (ACTIVATE-T): a multicentre, open-label, single-arm, phase 3 trial
Authors: Andreas Glenthøj, Eduard J van Beers, Hanny Al-Samkari, Vip Viprakasit, Kevin H M Kuo, Frédéric Galactéros, Satheesh Chonat, John Porter, Erin Zagadailov, Rengyi Xu, Abdulafeez Oluyadi, Peter Hawkins, Sarah Gheuens, Vanessa Beynon, Wilma Barcellini
Journal: The Lancet Haematology (2022)
Inferring Epistasis from Genetic Time-series Data
Authors: Muhammad Saqib Sohail, Raymond H Y Louie, Zhenchen Hong, John P Barton, Matthew R McKay
Journal: Molecular Biology and Evolution (2022)

Abstract Epistasis refers to fitness or functional effects of mutations that depend on the sequence background in which these mutations arise. Epistasis is prevalent in nature, including populations of viruses, bacteria, and cancers, and can contribute to the evolution of drug resistance and immune escape. However, it is difficult to directly estimate epistatic effects from sampled observations of a population. At present, there are very few methods that can disentangle the effects of selection (including epistasis), mutation, recombination, genetic drift, and genetic linkage in evolving populations. Here we develop a method to infer epistasis, along with the fitness effects of individual mutations, from observed evolutionary histories. Simulations show that we can accurately infer pairwise epistatic interactions provided that there is sufficient genetic diversity in the data. Our method also allows us to identify which fitness parameters can be reliably inferred from a particular data set and which ones are unidentifiable. Our approach therefore allows for the inference of more complex models of selection from time-series genetic data, while also quantifying uncertainty in the inferred parameters.
Improving biobehavioral health in younger breast cancer survivors: Pathways to Wellness trial secondary outcomes
Authors: Julienne E Bower, Ann H Partridge, Antonio C Wolff, Steve W Cole, Michael R Irwin, Elissa D Thorner, Hadine Joffe, Laura Petersen, Catherine M Crespi, Patricia A Ganz
Journal: JNCI Journal of the National Cancer Institute (2022)

The Pathways to Wellness trial tested the efficacy of 2 interventions for younger breast cancer survivors: mindful awareness practices (MAPs) and survivorship education (SE). This planned secondary analysis examines intervention effects on stress, positive psychological outcomes, and inflammation (Clincaltrials.gov NCT03025139).
Evolution of DNA base composition under no-strand-bias conditions when the substitution rates are not constant
Authors: J. R. Lobry, C. Lobry
Journal: Molecular Biology and Evolution (1999)

The evolution of DNA base composition evolution is simplified to a six-parameter model when there are no strand biases for mutation and selection. We analyzed the dynamics of this model with special attention to the influence of a change in substitution rates. The G + C content of the DNA sequence tends to an equilibrium value that is controlled by four parameters of the model. When the substitution rates are not constant, the G + C equilibrium position is not constant. The DNA sequence base frequencies always tend to a state in which A = T and G = C within a strand, regardless of substitution rates. This is true even when the substitution rates are not constant over time. This provides a simple way of rejecting the model from inspection of present-day DNA base composition.
Silmitasertib plus gemcitabine and cisplatin first‐line therapy in locally advanced/metastatic cholangiocarcinoma: A Phase 1b/2 study
Authors: Mitesh J. Borad, Li‐Yuan Bai, Donald Richards, Kabir Mody, Joleen Hubbard, Sun Young Rha, John Soong, Daniel McCormick, Emmett Tse, Daniel O'Brien, Ahmad Bayat, Daniel Ahn, S. Lindsey Davis, Joon Oh. Park, Do‐Youn Oh
Journal: Hepatology (2022)

Background and Aims: This study aimed to investigate safety and efficacy of silmitasertib, an oral small molecule casein kinase 2 inhibitor, plus gemcitabine and cisplatin (G+C) versus G+C in locally advanced/metastatic cholangiocarcinoma. Approach and Results: This work is a Phase 1b/2 study (S4‐13‐001). In Phase 2, patients received silmitasertib 1000 mg twice daily for 10 days with G+C on Days 1 and 8 of a 21‐day cycle. Primary efficacy endpoint was progression‐free survival (PFS) in the modified intent‐to‐treat population (defined as patients who completed at least one cycle of silmitasertib without dose interruption/reduction) from both phases (silmitasertib/G+C n = 55, G+C n = 29). The response was assessed by Response Evaluation Criteria in Solid Tumors v1.1. The median PFS was 11.2 months (95% confidence interval [CI], 7.6, 14.7) versus 5.8 months (95% CI, 3.1, not evaluable [NE]) ( p = 0.0496); 10‐month PFS was 56.1% (95% CI, 38.8%, 70.2%) versus 22.2% (95% CI, 1.8%, 56.7%); and median overall survival was 17.4 months (95% CI, 13.4, 25.7) versus 14.9 months (95% CI, 9.9, NE) with silmitasertib/G+C versus G+C. Overall response rate was 34.0% versus 30.8%; the disease control rate was 86.0% versus 88.5% with silmitasertib/G+C versus G+C. Almost all silmitasertib/G+C (99%) and G+C (93%) patients reported at least one treatment emergent adverse event (TEAE). The most common TEAEs (all grades) with silmitasertib/G+C versus G+C were diarrhea (70% versus 13%), nausea (59% vs. 30%), fatigue (47% vs. 47%), vomiting (39% vs. 7%), and anemia (39% vs. 30%). Twelve patients (10%) discontinued treatment because of TEAEs during the study. Conclusions: Silmitasertib/G+C demonstrated promising preliminary evidence of efficacy for the first‐line treatment of patients with locally advanced/metastatic cholangiocarcinoma.
Extracorporeal photopheresis in acute and chronic steroid‑refractory graft-versus-host disease: an evolving treatment landscape
Authors: Hildegard T. Greinix, Francis Ayuk, Robert Zeiser
Journal: Leukemia (2022)

Abstract Patients with steroid-refractory graft-versus-host disease (GvHD) are known to have a poor prognosis and for decades no approved drug has been available to treat this serious condition. Although ruxolitinib, a selective Janus kinase (JAK)1/2 inhibitor demonstrated significantly higher response rates in randomized trials compared to the best available therapy, and thus, is of benefit in both acute as well as chronic GvHD, there is an urgent medical need to improve results, such as durability of responses, response in eye, liver and lung manifestations and reduction of infectious complications. In this “Review” article we would like to offer strategies for improving treatment results in patients with steroid-refractory GvHD by combining ruxolitinib with extracorporeal photopheresis (ECP), a leukapheresis-based immunomodulatory treatment frequently applied in T-cell mediated immune disease including GvHD. Our article explores key published evidence supporting the clinical efficacy of both ruxolitinib and ECP in the treatment of GvHD and highlights their potentially complementary mechanisms of action.
The Uterine Blush
Authors: D FINK-BENNETT
Journal: Clinical Nuclear Medicine (1982)

To determine the presence, prevalence, and clinical importance of Tc-99 pertechnetate uterine uptake, this retrospective analysis of 71 Meckel's scans was undertaken. Specifically, each study was evaluated for the presence of a focal accumulation of radiotracer cephalad to the bladder. Patients received an intravenous dose of 150 µCi/kg of Tc-99 pertechnetate. Each study consisted of 15 one minute anterior serial gamma camera images, and a 15, 30, and 60 minute anterior, right lateral and posterior scintiscan. Menstrual histories were obtained from all patients except two. No males (33/33), nor premenstrual (13/13), menopausal (4/4) or posthysterectomy (2/2) patients revealed a uterine blush. Eleven of 15 patients (73%) with regular menses demonstrated a uterine blush. They were in the menstrual or secretory phases of their cycle. Four demonstrated no uterine uptake, had regular periods, but were in the proliferative phase of their cycle. Two with irregular periods, and one with no recorded menstrual history, manifested the blush. Radiotracer should be expected in the uterus during the menstrual and secretory phases of the menstrual cycle. It is a manifestation of a normal physiologic phenomenon, and must be recognized to prevent false-positive Meckel's scan interpretations.